This work involves development of a facile systematic method for isolating cell surface proteins unique to transformed animal cells. Our proposed procedure for the isolation of cell surface protein involves synthesis of macromolecular reagents consisting of a) a reactive group capable of forming a specific covalent bond with proteins; b) a macromolecular carrier, and c) a linkage between the two that is stable under normal physiological conditions, but may be selectively broken. The reactive group can be designed with many variations in specificity. Reagents directed toward thiol groups and amino groups, are being studied at this time. Proteins released from the macromolecular reagent will be purified further by gel filtration, electrophoresis, and ion exchange chromatography. Interactions of trypsin with animal cells in tissue culture are also being studied with the goal of gaining further insight concerning the modulation of cytoskeletal structure by interactions at the plasma membrane. Lastly, macromolecular substrates for proteolytic enzymes will be prepared in order to determine the expression of proteolytic enzymes on cell surfaces during cell growth and transformation.